title: Deleterious consequences of antioxidant supplementation on lifespan in a wild-derived mammal.
abstract: While oxidative damage owing to reactive oxygen species (ROS) often increases with advancing age and is associated with many age-related diseases, its causative role in ageing is controversial. In particular, studies that have attempted to modulate ROS-induced damage, either upwards or downwards, using antioxidant or genetic approaches, generally do not show a predictable effect on lifespan. Here, we investigated whether dietary supplementation with either vitamin E (α-tocopherol) or vitamin C (ascorbic acid) affected oxidative damage and lifespan in short-tailed field voles, Microtus agrestis. We predicted that antioxidant supplementation would reduce ROS-induced oxidative damage and increase lifespan relative to unsupplemented controls. Antioxidant supplementation for nine months reduced hepatic lipid peroxidation, but DNA oxidative damage to hepatocytes and lymphocytes was unaffected. Surprisingly, antioxidant supplementation significantly shortened lifespan in voles maintained under both cold (7 ± 2°C) and warm (22 ± 2°C) conditions. These data further question the predictions of free-radical theory of ageing and critically, given our previous research in mice, indicate that similar levels of antioxidants can induce widely different interspecific effects on lifespan.
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen AB24 2TZ, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Selman
authors.forename: Jane S
authors.initials: JS
authors.lastname: McLaren
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Collins
authors.forename: Garry G
authors.initials: GG
authors.lastname: Duthie
authors.forename: John R
authors.initials: JR
authors.lastname: Speakman
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D003411:Arvicolinae / Q000502:physiology*; D001205:Ascorbic Acid / Q000008:administration & dosage*; D001481:Basal Metabolism / Q000187:drug effects; D003080:Cold Temperature; D019587:Dietary Supplements; D005260:Female; D008136:Longevity / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D024502:alpha-Tocopherol; D001205:Ascorbic Acid
keywords: ageing; longevity; oxidative damage; vitamin C; vitamin E; vole